Pediatric emergency medicine trisk 1874 1874
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sources, glycogenolysis and gluconeogenesis, and glucose use by muscle, heart, adipose tissue,
brain, and blood elements. The liver plays a unique role in glucose homeostasis because it
stores glucose as glycogen. With fasting, this glycogen is degraded to glucose, which is
released into the bloodstream. In addition, the liver synthesizes new glucose from glycerol,
lactate, and certain amino acids. During fasting, lipolysis occurs, and the resultant fatty acids
are used for the production of both energy and ketones (acetoacetate and β-hydroxybutyrate)
by the liver. The energy generated from the metabolism of fatty acids is essential to sustain
maximal rates of gluconeogenesis and ureagenesis in the liver. The ketones are an important
auxiliary fuel for most tissues, including the brain. Muscle contains significant quantities of
glycogen and protein. Under fasting conditions, the glycogen is degraded and used
endogenously but is not released as free glucose into the bloodstream. Certain amino acids,
particularly alanine and glycine, are released from the muscle and subsequently used by the
liver for gluconeogenesis. Muscle derives an increasing proportion of its energy requirement
from fatty acids as fasting proceeds. Brain tissue is highly dependent on glucose for its energy
requirements. Under certain circumstances, it can extract a limited proportion of its energy
requirement from other substrates (e.g., glycerol, ketones, lactate), although this process
requires a period of adaptation and does not obviate the need for a constant supply of glucose.
Insulin is the primary hormone that regulates the blood glucose level. Insulin stimulates the
uptake of glucose and amino acids into skeletal, cardiac, and adipose tissue and promotes
glycogen and protein synthesis. It inhibits lipolysis and glycogenolysis. The net effect of
insulin action is to accelerate the removal of glucose and gluconeogenic substrates from the
bloodstream. Opposing or modulating the effects of insulin are cortisol, glucagon, epinephrine,
and growth hormone. The effects of these hormones include inhibition of glucose uptake by
muscle, mobilization of amino acids for gluconeogenesis, activation of lipolysis, inhibition of
insulin secretion, and induction of gluconeogenic enzymes. The net effect is to increase the
availability of gluconeogenic substrates to the liver, and to increase the accessibility and use of
nonglucose fuels by other tissues.
